Pharmacologic studies on the muscarinic cholinergic receptors of iris sphincter obtained from the atropine esterase plus ve and minus ve animals are planned. The influence of pigmentation, if any, will be investigated by comparative study in the pigmented and nonpigmented iris. Although pigment cells appear to bind the neurotransmitter, the kinetic details of the release and extraneuronal uptake of the transmitter in relation to the enzymatic activity will be investigated. Many neurotransmitter-related drugs influence the electroretinogram of rabbits. Well-known receptor stimulants and blockers will be used to analyze the drug effects on the ERG in both albino and nonalbino rabbits. Ototoxicity of many antibiotics, aminoglycosides like neomycin, kanamycin and gentamicin, is at least in part equated with drug binding by the inner ear melanin. Details of kinetics of binding of selected aminoglycoside on the isolated melanins and melanin granules will be studied to understand the relevancy of binding to the toxicity.